Separately packaged applicator pads for topical delivery of incompatable drugs

ABSTRACT

The present invention provides a method for applying a plurality, preferably two, dermatological agents to the skin from a single dispensing and applicator system comprising a plurality of compartmentalized applicator pads which may be exposed and sequentially applied to the afflicted skin area.

FIELD OF THE INVENTION

The invention is directed to a method for containing protecting,dispensing and applying substances such as solid and flowing substances,and more particularly, to a method for dispensing and applying two ormore dermatological agents either simultaneously or sequentially.

BACKGROUND OF THE INVENTION

A wide variety of packages are used to contain and protect a substanceuntil it is desired to release and dispense the substance from thepackage. Several methods exist for dispensing and applying various solidsubstances or articles, such as powders, pills, granules and othershaped substances. Said methods may also be used to dispense and applyvarious flowable substances such as gels, solutions, dispersions, andother dimensionally unstable substances. In some cases, it may bedesirable to include structure as part of the package which assists indispersing or applying the contents. Oftentimes, the package includes anapplicator for directed application of the contents, as they aredispensed from the package.

Several factors are taken into consideration in providing a method fordispensing a flowable or solid substance. One concern is the performancecharacteristics of the dispensing package. For example, the ease withwhich the package can be opened and its contents expelled can beimportant. The ability of the package to store and contain a substanceprior to its application is another factor. When an applicator such asan absorbent pad or sheet is included as part of the package, secureattachment of the applicator to the packaging can be important so thatthe applicator does not become disengaged during use.

Various packages have been developed to contain and dispense solutions,dispersions or gels of various active ingredients. One such dispenser isan envelope-like package that defines an internal reservoir forcontaining a fluid. For example, U.S. Pat. No. 4,427,115 to Laipply,discloses a packaging device for applying various fluids to the skin.The device is made of a flexible sheet of fluid impermeable materialthat is folded in half and sealed around the edges in a temporary seal.The two halves of the sheet are pulled apart to break the seal and forma flat surface covered with the fluid. An absorbent pad may be adheredinside the chamber to aid in the retention and delivery of the fluid.

Other packaging systems provide for a cup-like reservoir with a foil orpaper covering that is torn off to expose the fluid or other materialcontained within the chamber. For example, Canadian Patent No. 613,023to Wilson et al. discloses a creamer-type dispenser with a wide-mouthedcup and a covering sheet sealed over the mouth of the cup. The coveringsheet has a tab adhesively sealed over a flat extension of the rim ofthe cup. The package is opened by pulling the tab of the covering sheetupward off the rim extension and inward toward the cup. U.S. Pat. No.3,860,348 to Doyle et al. discloses a cup with a foil covering over themouth and a liquid-impregnated sponge attached to the inside of the cup.When the covering is peeled off the rim of the cup, the sponge projectsoutward through the opening.

U.S. Pat. No. 4,372,098, to Mason discloses an applicator package with apair of side panels, one of which has a recessed portion for receivingan absorbent pad which is secured to the side panel within the centralrecessed portion. The applicator means sealed within the package bysealing the edged portion of the side panel in surrounding relation tothe applicator means thereby enclosing and hermetically sealing theapplicator means within the side panels. One of the edged portions ofthe side panels is then secured to enable the side panels to be grippedat that area and separated from each other so as to expose theapplicator means.

Packages have also been developed to expel the contents of an innerchamber through a fracture or score line in one surface of the package.The ends of the package are forced together to expand and rupture thescore line. For example, U.S. Pat. No. 3,968,630 to Redmond discloses adispensing package having a single reservoir with a pattern ofperforations cut partially through the surface on one side of thepackage that is covered with a foil sealant.

U.S. Pat. No. 4,796,751 to Madkour discloses a portable eyeglasscleaning kit which comprises a generally flat flexible container havingtwo separate compartments which are separably operable to make separablyavailable the lens cleaning medium and the lens wiping medium. Thecleaning and wiping media absorbent material such as woven or unwovenfabric or tough liquid absorbent paper. The cleaning and wiping mediaare not affixed to the container and are separably removable from thecompartments of the container. The container is made of a moisture andgas impervious sheet material such as metal foil, treated paper orplastic film. the container is operable by tearing along a scored lineor by separation of the sealed edges.

A further consideration in designing a useful dispensing system is theability to deliver more than one substance from a unitary system. Alsodesirable is a packaging system that is useful to simultaneously combineand dispense a plurality of substances, each requiring separate storageuntil being combined, due to their physical or chemical incompatibility.

To accomplish this, several applicator systems with a prescored fractureline in one surface of a package provide for reservoirs in discreteportions of a single package. For example, U.S. Pat. No. 4,140,409 toDeVries discloses a package system for containing and dispensing liquidsand other flowable materials comprising a reservoir chamber in each halfof an elongated package. A prescored fracture line in one surface of thepackage ruptures when the ends of the package are urged together, andthe contents of the chambers are expelled into an applicator sponge thatis attached to the outside of the package. However, a disadvantage ofpackages with such externally placed applicators is that the applicatormay become soiled or detached. Also, where a sterile applicator isdesired, such a package system may not maintain the applicator undersanitary conditions prior to use.

A covering may be provided to enclose an externally attached applicator.For example, U.S. Pat. No. 4,430,013 to Kaufman discloses a packagesystem that has an interior chamber for containing a fluid, a score linein one surface of the package, and an applicator mounted over the scoreline. An overwrap with a fracture line on one surface encloses thepackage and the applicator. When the package is folded in half, thescore line is broken and the fluid in the reservoir chamber is expelledinto the applicator. The applicator then bursts through the fractureline in the overwrap.

In accordance with this packaging system, the liquid substance iscontained and stored within a reservoir separately from the applicatoruntil the package is opened. A drawback of this system is that todispense the substance from the package, the reservoir chamber mustfirst be opened, and the substance must be ejected therefrom and thendispersed into and through the applicator, which can result in unevenwetting of the applicator. In addition, problems may occur because ofpremature leakage or evaporation of the liquid contents from the innerchamber of the dispensing package into the external applicator due to apremature break in the fracture line. If the overwrap becomes torn orpunctured, the applicator may become uncovered and contaminated, and theliquid substance prematurely dispensed.

To provide a more secure containment, the applicator may be enclosedwithin a more rigid package. Kaufman also discloses a package system inwhich an applicator is attached to the inside of a package that has ascore line on one surface. The applicator is compressible andsponge-like with a protruding thickened portion placed against the scoreline. A rib projection is provided on the inside surface of the packageopposite the score line to help push the applicator out through thescore line when the package is folded. A drawback is that the packagecannot be reclosed or resealed with the applicator contained inside oncethe fracture line is separated and the applicator extruded.

U.S. Pat. No. 4,812,067 to Brown et al. also provides a system thatprovides separate reservoir chambers in a flexible package. The chambersare compressed to rupture an internal seal in the package which urgesthe liquid contents into a central dispensing cavity. The ends of thepackage are bent backward to split open a score line in the surface ofthe package. Pressure on the package forces the contents to be expelledthrough the slit in the score line and onto a sponge attached to theoutside of the package.

A disadvantage of packaging devices that release their contents byrupturing a score line in the container wall is that flexing of thepackage prior to use may cause the fracture line to split apartprematurely, thus causing unwanted leakage or premature dispersal of thecontents. Conversely, the score line may be constructed such that it isdifficult to break.

Therefore, there is a need for a method of dispensing system whichaddresses the above mentioned problems of prior dispensing systems. Inparticular, there is a need for a packaging system for dispensingflowable and/or solid substances which has an improved configuration forreleasing the contents of the packaging that is not prone to prematurerupture, but provides ready dispensing of the package contents. There isalso a need for a packaging that is a convenient means of dispensing aplurality of flowable and/or solid substances from multiple chamberswithin the packaging system, to overcome the physical or chemicalincompatibility of the substances, or to allow for sequentialapplication.

SUMMARY OF THE INVENTION

The present invention provides a novel method for containing, dispensingand applying two or more substances such as solids such as powders orgranules, and/or flowable substances such as gels, dispersions orsolutions.

In one embodiment of the invention there is provided a method forapplying a plurality of dermatological agents to the skin from onedispensing and applicator system comprising the steps of (1) providing adispensing and applicator system comprising a first and second flexible,moisture impermeable cover sheet; a first and second applicator pad eachaffixed to one surface of said first and second cover sheets,respectively; each of said pads being impregnated with a compositioncomprising a different dermatological agent; and a flexible, moistureimpermeable support sheet having its peripheral surface on its firstside releasably sealed to the opposed peripheral surface of the firstcover sheet so as to form a first compartment defined by a firstcontinuous seal, and containing the first pad; and said support sheethaving its peripheral surface on its second side releasably sealed tothe opposed peripheral surface of the second cover sheet so as to form asecond compartment defined by a second continuous seal and containingsaid second pad. The first and second seals are positioned inwardly fromthe edges of the sheets over a portion of the opposed peripheralsurfaces, so as to form a pair of two opposed flanges; (2) sequentiallymanually grasping and separating each pair of flanges to at leastpartially release each cover sheet from the support sheet, so that saidpads are exposed; and (3) contacting the pads with the skin to releasethe compositions sequentially from the pads, so as to apply a film ofthe agents onto the skin.

In another embodiment of the invention there is provided a method forapplying a plurality of dermatological agents to the skin from onedispensing and applicator system comprising the steps of: (1) providinga dispensing and applicator system comprising a first and secondflexible, moisture impermeable cover sheet; a first and secondapplicator pad affixed to a first surface of said first and second coversheets, respectively; each of said pads being impregnated with a firstand a second composition, respectively, each composition comprising adifferent dermatological agent; and a flexible, moisture impermeablesupport sheet having one peripheral surface releasably sealed to a firstopposed peripheral surface of the first cover sheet so as to form afirst compartment containing the first pad attached to said firstsurface of first cover sheet, and said second cover sheet having itsfirst peripheral surface releasably sealed to the opposed secondperipheral surface of the first cover sheet so as to form a secondcompartment containing said second pad attached to said first surface ofsaid second cover sheet, each releasable seal defined by a continuousseal, which seal is positioned inwardly from the edges of the sheetsover a portion of the opposed peripheral surfaces, so as to form a pairof two opposed flanges; (2) sequentially manually grasping andseparating each pair of the flanges to at least partially release thesecond cover sheet from the first cover sheet and the first cover sheetfrom the support sheet, so that said pads are exposed; and (3)contacting the pads with the skin to release the compositionssequentially from the pads, to thereby apply a film of the agents ontothe skin.

In still another embodiment of the invention there is provided a methodfor applying a plurality of dermatological agents to the skin from onedispensing and applicator system comprising the steps of (1) providing adispensing and applicator system comprising a flexible, moistureimpermeable support sheet having a first and a second surface, andhaving a first applicator pad affixed to the first surface of thesupport sheet, and a second application pad affixed to the secondsurface of the support sheet, each of the pads being impregnated with acomposition comprising a different dermatological agent in combinationwith a compatible carrier; wherein the first pad is covered by aflexible, moisture impermeable first cover sheet; and the second pad iscovered by a flexible, moisture impermeable second cover sheet, eachcover sheet having a peripheral surface releasably sealed to the opposedperipheral surface of the support sheet so as to form a compartmentcontaining a pad and defined by a continuous seal, each seal beingpositioned inwardly from the edge of the support sheet and the edge ofeach cover sheet over a portion of the opposed peripheral surfaces, soas to form a pair of two opposed flanges; (2) sequentially manuallygrasping and separating each pair of flanges to at least partiallyrelease each cover sheet from the support sheet, so that the pads aresequentially exposed; and (3) contacting the pads with the skin torelease the compositions sequentially from the pad, to thereby apply afilm of the agents onto the skin.

For example, the present applicator system is particularly well-adaptedto contain, preserve and to sequentially or simultaneously deliver twoor more chemically or physically incompatible active ingredients.Preferably, the two-pad applicator will be used to contain, preserve anddeliver unit doses of two cosmetic or pharmaceutical ingredientsintended for topical application to the skin, e.g., dermatologicalagents, such as are used to treat a disorder such as acne, dermatitisincluding atopic dermatitis, insect bites, diaper rash, sunburn, burns,eczema, psoriasis, poison ivy rash, poison oak rash, poison sumac rash,rashes or other skin irritation due to cosmetics, detergents or jewelryand the like.

Novel dispensing and applicator systems are also within the scope of theinvention.

As used herein, the term "dermatological agent" includes bioactivesubstances such as antibiotics and peroxides, as well as compoundsintended primarily for cosmetic purposes, such as emollients andsunscreens.

All percentages are by weight unless otherwise indicated.

These and other advantages of the invention over conventional dispensingand application methods will become more apparent after reading thedescription and claims which follow.

BRIEF DESCRIPTION OF THE DRAWINGS

Throughout the following views, reference numerals will be used on thedrawings, and the same reference numerals will be used throughout theseveral views and in the description to indicate same or like parts ofthe invention.

FIG. 1 is a perspective view of a first embodiment of the dispensingdevice of the invention shown in the closed position.

FIG. 2 is a perspective view of a first embodiment of the dispensingdevice of the invention shown with the first and second cover sheetspartially removed.

FIG. 3 is a perspective view of a second embodiment of the dispensingdevice of the invention shown in the closed position.

FIG. 4 is a perspective view of a second embodiment of the dispensingdevice of the invention shown with the first cover sheet partiallyremoved.

FIG. 5 is a perspective view of a second embodiment of the dispensingdevice of the invention shown with the first cover sheet removed and thesecond cover sheet partially removed.

FIG. 6 is a perspective view of a third embodiment of the dispensingdevice of the invention shown in the closed position.

FIG. 7 is a perspective view of a third embodiment of the dispensingdevice of the invention shown with first and second cover sheetsremoved.

DETAILED DESCRIPTION OF THE INVENTION

Referring now to FIGS. 1 and 2, a first embodiment of the dispensing andapplicator device, designated generally by the numeral 10, is shownaccording to the present invention. The dispensing and applicator device10 is shown having a first cover sheet 12, a second cover sheet 13 and asupport sheet 14. The first and second cover sheets 12, 13 haveperipheral surfaces 30, 31 extending completely around the first andsecond cover sheets 12, 13, respectively. Support sheet 14 hasperipheral surfaces 32, 33 extending completely around the first andsecond surfaces 16, 18 of support sheet 14. Integral with peripheralsurfaces 30, 31 of cover sheets 12, 13 are flanges 60, 61 and integralwith peripheral surfaces 32, 33 of support sheet 14 is flange 62.Flanges 60, 61 and 62 are used for gripping in order to separate firstand second cover sheets 12, 13 from support sheet 14 to open thedispensing and applicator device 10.

Applicator pads 20, 22 are positioned on the surfaces of cover sheets12, 13 which oppose the surfaces 16, 18 of the support sheet 14.Optionally, recessed areas (not shown) may be provided in cover sheets12, 13 to receive applicator pads 20, 22. Applicator pads 20, 22 areattached to the surface of cover sheets 12, 13 by known techniques inthe art. In order to enclose the applicator pads 20, 22 within thedispensing and applicator device 10, the peripheral edges 30, 31 offirst and second cover sheets 12, 13, and peripheral edges 32, 33 ofsupport sheet 14 are releasably sealed together, respectively, insurrounding relation to applicator pads 20, 22, by seal lines 34, 35,thereby defining two compartments within which the applicator pads 20,22 are enclosed and sealed. Any suitable means of forming real lines 34,35, such as those discussed below, may be utilized.

The flanges 60, 61 of first and second cover sheets 12, 13 and flange 62support sheet 14 are created by positioning the seal lines inward fromat least a pair of abutting edges of first and second cover sheets 12,13 and support sheet 14. Flanges 60, 61 provide a means for grippingfirst and second cover sheets 12, 13 and flange 62 provides a means ofgripping support sheet 14 to facilitate the opening of dispensing andapplicator device 10 by pulling first and second cover sheets 12, 13apart from support sheet 14 and thus sequentially or simultaneouslyexposing applicator pads 20, 22. While these flanges 60, 61, 62 areshown as extending the entire length of one edge of device 10, it isreadily apparent that flanges 60, 61, 62 could be provided over a morelimited area, such as only at one corner of first and second coversheets 12, 13 and support sheet 14.

Referring now to FIGS. 3, 4 and 5, a second embodiment of the dispensingand applicator device, designated generally by the numeral 10, is shownaccording to the present invention. The dispensing and applicator device10 is shown having a first cover sheet 12, a second cover sheet 13 and asupport sheet 14. The first and second cover sheets 12, 13 haveperipheral edges 30, 31 extending completely around the first and secondcover sheets 12, 13, respectively. Support sheet 14 has peripheral edge32 extending completely around support sheet 14. Integral withperipheral edges 30, 31 of cover sheets 12, 13 are flanges 60, 61 andintegral with peripheral edge 32, of support sheet 14 is flange 62.Flanges 60, 61 and 62 are used for gripping in order to separate firstand second cover sheets 12, 13 from support sheet 14 to open thedispensing and applicator device 10.

First and second applicator pads 20, 22 are on positioned on one surfaceof first and second cover sheets 12, 13, respectively. Optionally,recessed areas (not shown) may be provided in cover sheets 12, 13 toreceive applicator pads 20, 22. Applicator pads 20, 22 are attached tothe surface of cover sheets 12, 13 by known techniques in the art. Inorder to enclose first applicator pad 20, within the dispensing andapplicator device 10, peripheral edge 30 on the side of first coversheet 12 to which first applicator pad 20 is affixed is releasablysealed to opposed peripheral edge 32 of support sheet 14 by means ofseal line 34, which is positioned in surrounding relation to firstapplicator pad 20; thereby defining a compartment within which firstapplicator pad 20 is enclosed and isolated. In order to enclose secondapplicator pad 22, within the dispensing and applicator device 10,peripheral edge 31 on the side of second cover sheet 13 to which secondapplicator pad 22 is affixed is releasably sealed to opposed peripheraledge of the first cover sheet 12 which is opposite to edge 30, by meansof seal line 36, which is positioned in surrounding relation to secondapplicator pad 22; thereby defining a compartment within which secondapplicator pad 22 is enclosed and isolated. Any suitable means ofsealing, such as those discussed below, may be utilized.

The flanges 60, 61 of first and second cover sheets 12, 13 and flange 62support sheet 14 are created by positioning the seals 37, 36 inward fromat least a pair of abutting edges of first and second cover sheets 12,13 and support sheet 14. Flanges 60, 61 provide a means for grippingfirst and second cover sheets 12, 13 and flange 62 of provides a meansof gripping support sheet 14 to facilitate the opening of dispensing andapplicator device 10 by pulling first cover sheet 13 apart form secondcover sheet 12, and second cover sheet 12 apart from support sheet 14,thus exposing applicator pads 22, 20, respectively. While these flanges60, 61, 62 are shown as extending the entire length of one edge ofdevice 10, it is readily apparent that 60, 61, 62 flanges could beprovided over a more limited area, such as only at a corner of first andsecond cover sheets 12, 13 and support sheet 14.

Referring now to FIGS. 6 and 7, a third embodiment of the dispensing andapplicator device, designated generally by the numeral 10, is shownaccording to the present invention. The dispensing and applicator device10 is shown having a first cover sheet 12, a second cover sheet 13 and asupport sheet 14. The first and second cover sheets 12, 13 haveperipheral edges 30, 31 extending completely around the first and secondcover sheets 12, 13, respectively. Support sheet 14 has first and secondperipheral surfaces 32, 33 extending completely around the first andsecond surfaces of support sheet 14. Integral with peripheral edges 30,31 of cover sheets 12, 13 are flanges 60, 61 and integral withperipheral edges 32, 33 of support sheet 14 is flange 62. Flanges 60, 61and 62 are used for gripping for gripping in order to separate first andsecond cover sheets 12, 13 from support sheet 14 to open the dispensingand applicator device 10.

Applicator pads 20, 22 are on positioned on the opposite surfaces ofsupport sheet 14 by known techniques in the art. In order to enclose theapplicator pads 20, 22 within the dispensing and applicator device 10,the peripheral edges 30, 31 of first and second cover sheets 12, 13, andperipheral edges 32, 33 of support sheet 14 are releasably sealedtogether, respectively, in surrounding relation to applicator pads 20,22, by seal lines 37, 34, respectively, thereby defining twocompartments within which the applicator pads 20, 22 are enclosed andsealed. Any suitable means of sealing, such as those discussed below,may be utilized.

The flanges 60, 61 of first and second cover sheets 12, 13 and flange 62support sheet 14 are created by positioning the seals 37, 34 inward fromat least a pair of abutting edges of first and second cover sheets 12,13 and support sheet 14. Flanges 60, 61 provide a means for grippingfirst and second cover sheets 12, 13 and flange 62 provides a means ofgripping support sheet 14 to facilitate the opening of dispensing andapplicator device 10 by pulling first and second cover sheets 12, 13apart from support sheet 14 and thus exposing applicator pads 20, 22.While these flanges 60, 61, 62 are shown as extending the entire lengthof one edge of device 10, it is readily apparent that 60, 61, 62 flangescould be provided over a more limited area, such as only at a corner offirst and second cover sheets 12, 13 and support sheet 14.

As depicted in FIGS. 1 through 7, dispensing and applicator device 10 isof a generally rectangular configuration. It will be understood,however, that a variety of shapes and sizes can be accommodatedaccording to the invention.

Applicator pads 20, 22 may be made, for example, of a natural orsynthetic, woven or nonwoven fiber, such as gauze, felt, cotton, or fromplastic foam or sponge. Other woven or nonwoven material capable ofabsorbing a liquid or flowable composition may be used. Anotherapplicator useful according to the invention is, for example, a sheet ofplastic or stiff paper having pores through which a powder or granularsubstance, or flowable substance, may be dispensed.

The material used for cover sheets 12, 13 and support sheet 14 should berelatively puncture resistant, non-absorbent, and impermeable,chemically compatible and non-reactive with the flowable substance ormaterial contained in the dispensing and applicator device 10 to preventleakage or migration of the contents out of the dispensing andapplicator device 10, and substantially impermeable to externalcontaminants such as air, dust, liquids and the like.

Suitable materials for cover sheets 12, 13 and support sheet 14 shouldbe materials capable of allowing cover sheets 12, 13 to be sealed tosupport sheet 14 along the seal lines in order to form a containing anddispensing package that does not separate during normal use. Forexample, cover sheets 12, 13 and support sheet 14 may be made of athermoplastic and heat sealable polymeric film material, such aspolyethylene, polyvinyl chloride, or polyamide-type resins, according toknown techniques in the art. Such a film may be used alone or adhered toa non-heat sealable material by known techniques. Cover sheets 12, 13and support sheet 14 may be formed, for example, of glassine paper,cellophane, polyethylene, polypropylene, polyvinyl chloride, polyester,nylon and the like. Cover sheets 12, 13 and support sheet 14 may also beformed of an aluminum foil that is coated or sealed with a thermoplasticmaterial such as a polyethylene, polyester, polyvinyl resin or celluloseacetate. Alternatively, the foil may comprise a cellulosic materiallined with a thermoplastic film or other synthetic or plastic material.A foil-lined paper board may also be used. For examples of flexiblematerials suitable for cover sheets 12, 13 and support sheet 14, see forexample, "Coatings and Laminations," in Handbook of Package Engineering(2d ed.), pages 4-1 to 4-20, J. F. Hanlon, the disclosure of which isincorporated by reference herein.

Cover sheets 12, 13 and support sheet 14 may also be formed of alaminate or covered with a lamination that includes components such asfluorohalocarbon (Aclar), cellulose acetate, cellophane, polyester,polyvinyl chloride (PVC), polyethylene (PE), polypropylene, rubberhydrochloride, PVDC, and the like. A laminated cover sheets 12, 13 andsupport sheet 14 may include, for example, paper or foil with polyester,acetate with foil and lacquer, acetate with metallized Mylar andpolyester, and other suitable combinations that will provide, forexample, a stiff yet flexible cover sheets 12, 13 and support sheet 14,a moisture or gas barrier, protection of the contents from photochemicalchange from exposure to light, prevention of plasticizers andstabilizers from the film by the contents of the package, and other likefactors. For example, cover sheets 12, 13 and support sheet 14 may beformed of a laminated paper board material such as a stiff cardboardthat is covered with a foil material and/or a structured film. Thelayers of the lamination may be sealed together, as for example, byheat.

A coating to provide a nonporous gas and/or vapor barrier, as forexample polyethylene and/or polyester, may be applied to the outersurface of cover sheets 12, 13 and support sheet 14. The coating mayprovide a sealant to prevent entry of vapors or water, or evaporation ofthe contents from dispensing and applicator device 10, such as anorganic solvent vehicle. Cover sheets 12, 13 and support sheet 14 may becoated, for example, with a wax coating such as a paraffin wax alone oras part of a blend, as for example, with microcrystalline wax andpolyethylene; a varnish coating; a polyvinylidene chloride (PVDC)coating; a polyester (PET) coating, as for example, polyethyleneterephtalate; a heat seal coating, as for example, with polyethylene,vinyl, acetate, polyvinyl resin or cellulose acetate, or othercellulosics, or polyvinyl chloride; an extrusion coating, as forexample, with polyethylene; or a metallized film coating, as forexample, a metallized polyester, nylon, polyethylene, or polypropylenehaving a thin layer of aluminum. A coextruded or composite film may alsobe used to cover sheets 12, 13 and support sheet 14. A composite filmmay include, for example, polyethylene and polypropylene with nylon,EVA, saran, and/or styrene.

As stated above, support sheet 14 may be made of the same or similarmaterial as that used for cover sheets 12, 13, but preferably supportsheet 14 is somewhat more rigid than cover sheets 12, 13. For example,support sheet 14 may additionally be made of synthetic organic polymericsheet material such as polystyrene, acrilonitride or acrylic copolymerwith polystyrene, for example by extrusion, thermoforming,vacuum-forming, or other technique known in the art. A coating toprovide a nonporous gas and/or vapor barrier, as for example, a coating,a co-extruded plastic such as polyethylene and polyethyleneterephtalate, or a laminate of these materials and others such aspolypropylene, polyvinylidene chloride, cellophane, and the like, may beapplied to the outer surface of support sheet 14 as a sealant to prevententry of vapors or water, or evaporation of the contents of dispensingand applicator device 10, such as an organic solvent.

Cover sheets 12, 13 may be sealed to support sheet 14 by a heat seal,pressure seal, high frequency seal, ultrasonic seal, a crimp, a bondingmaterial or by means of various adhesive materials. Other suitableattachment methods or means may be used to effect a secure sealaccording to known techniques in the art. For example, heat may beapplied according to known techniques in the art to cause a bonding ofthe thermoplastic liner of support sheet 14 to cover sheets 12, 13. Atemporary heat seal may be formed by applying relatively narrow lines ofheat seal, and wider lines of heat seal may be applied to effect a morepermanent seal. A permanent seal may also be provided by applying a highdegree of heat using an appropriately high temperature, and a lowerdegree of heat using a lower temperature to provide a temporary seal.

Adhesives used to form the seal lines should be non-reactive andcompatible with the materials used for cover sheets 12, 13 and supportsheet 14 as well as with the contents within the compartment orsubcompartments of dispensing and applicator device 10, and should notpermit premature leakage or diffusion of such materials from thepackage. An example of adhesives for effecting a releasable sealinclude, for example, polyvinyl chloride (PVC) applied to one surface,and polyvinyl acetate applied to a second surface. Cover sheets 12, 13and support sheet 14 may also be sealed together by a piece of material(not shown) attached between cover sheets 12, 13 and support sheet 14.

It is understood according to the invention that applicator pads 20, 22may each contain the same or different substances. Advantageously, thedispensing and applicator device 10 of the invention may be used todispense two or more substances that should be, or are preferably, keptseparated until the desired application. The two components would thenbe dispensed according to the invention simultaneously by the twoapplicator pads 20, 22, or sequentially from one of the applicator pads20, 22 at a time. A wide variety of different cosmetic or bioactiveagents as those combinations set forth herein, may be impregnated inapplicator pads 20, 22.

Acne

Acne is a common inflammatory disease of human skin, and concentrates inskin areas where sebaceous glands are largest, most numerous, and mostactive. In its milder types, it is a more or less superficial disorderwhich is evidenced by slight, spotty irritations and ordinary skinhygiene is a satisfactory treatment. However, in the more inflammatorytypes of acne, bacterial invasion of or about the pilosebaceousfollicles occurs and pustules, infected cysts and, in extreme cases,canalizing inflamed and infected sacs appear. These lesions may becomeextensive and leave permanent, disfiguring scars.

To reduce the severity of acne, various forms of medication havepreviously been topically applied to the skin. Antibacterial soaps havebeen used as well as bactericidal agents such as sulfur and resorcinol.Other topical compositions have separately contained benzoyl peroxide,hexachlorophene, erythromycin or neomycin sulfate. None of these priorpreparations has been completely effective.

As disclosed by Klein et al. (U.S. Pat. No. 4,497,794), it wasdiscovered that a mixture on the skin of a peroxide, especially benzoylperoxide and an antibiotic or antibacterial such as clindamycin,neomycin, sodium sulfacetamide, sulfur, tetracycline or erythromycin isparticularly beneficial as they can exert a statistically significantsynergistic effect. Peroxides inhibit the formation of free fatty acidsin the skin, primarily through inactivation of extracellular lipase (viaoxidation) necessary to cleave triglycerides into free fatty acids andglycerol. The antibiotic or antibacterial component reduces theconcentration of Corynebacterium acnes (i.e., P. acnes), a normalanaerobic bacteria which is the prime source of the lipase. Instead ofthe benzoyl peroxide, which is preferred, peroxides such as stabilizedhydrogen peroxide and peroxides of organic acids, such as a lauroylperoxide, may be used.

As disclosed by Klein et al., erythromycin and benzoyl peroxide may beapplied to the skin in combination in a preformulated aqueous-alcoholicgel. However, if a mixture is first made up and then applied to theskin, it is best that the mixture be made at the time of application orthat the mixture be used within twenty-four hours. The prompt use of apremix is necessary due to the chemical incompatibility of the twoactive agents. Because of this, it is advisable that the two agents beput in separate vials, bottles or other containers. For example, theKlein et al. patent discloses a kit containing, separately bottledliquid compositions comprising 5% benzoyl peroxide and a solution oferythromycin in ethanol or acetone.

However, separately packaging multiple dosages of the two activeingredients presents a number of disadvantages to the end-user. Forexample, a unit application dosage of each active must be removedsequentially from each container and absorbed onto an applicator, suchas a cotton swab, so that it can be coated onto the skin of the user.This provides opportunities for spillage or over- or under-dosing, whichcan lead to skin irritation and other side effects. Furthermore, such amultidose system necessarily adds to the costs of packaging, shippingand storage.

As can readily be ascertained from the foregoing description, thedispensing and applicator system is intended to overcome thesedifficulties. As exemplified, the present dual-pad package can readilycontain, preserve and deliver single unit doses of two or morechemically- or physically-incompatible active ingredients. For example,an antibiotic in combination with a liquid, semi-liquid (cream) orgelled aqueous or non-aqueous vehicle can be absorbed by and retained bythe first pad and a second ingredient which is physically- orchemically-incompatible with the antibiotic, such as a peroxide, can beabsorbed and retained by the second pad, preferably in combination withthe appropriate vehicle.

Alternatively, the present application system can be used to contain andrelease two active ingredients which are desirably applied sequentially,whether or not they are physically or chemically compatible on the skin.Other examples of pairs of such ingredients include (a) an antibiotic orperoxide for treatment of a skin disorder and a keratolytic/antisepticagent such as salicylic acid; (b) retinoic acid (Retin® A) andmoisturizing agent to counteract the drying/scaling effects of theRetin® A, and/or a sunscreen to protect the skin against the increasedsensitivity to the sun caused by the Retin® A, (c) a pigmented,wax-based make-up composition, such as eye-shadow, blush, foundationbases and the like, or a sunscreen in a similar water-insoluble vehicle;and liquid make-up remover formulations that are formulated to removethe make-up or the sunscreen; and (d) a steroid, preferably acorticosteroid and a complementary dermatological agent, such as anantihistamine, antifungal, antibiotic and/or sunscreen.

As can be readily seen from the figures, the present applicator isadapted to sequentially release and produce in situ a mixture of two (ormore) active ingredients on the target skin area to be treated. Bothcover sheets can be removed, and the attached pads can be sequentiallyapplied to the skin area to be treated. Alternatively, the coveringsheets can be removed to expose the applicator pads, as it is desired toapply the active therefrom, e.g., at substantial intervals of time andto different areas of the skin, while leaving the remaining pad or padsenclosed.

Although each pad will contain at least one active ingredient,preferably in combination with a suitable carrier vehicle, compositionscontaining multiple active, chemically compatible ingredients can beabsorbed onto each of one or more of the pads.

COMPOSITIONS FOR ACNE TREATMENT I. Peroxide

One pad in the present acne-treatment applicator system will preferablycomprise an effective fatty-acid-inhibiting amount of a peroxide, i.e.,hydrogen peroxide or an organic peroxide, preferably in combination witha gelled or semiliquid (lotion or cream) vehicle.

No matter what vehicle is employed, on a weight basis, the selectedantibiotic (clindamycin, tetracycline and/or erythromycin) and theselected peroxide should be measured out so that as applied to the skin,the latter is from about one to about thirty times the weight of theformer, preferably from about one to about five times. Thus, on thefirst pad, the selected antibiotic should be present at a level rangingfrom 0.5% to 5.0% w/w of the total composition absorbed into the padand, on the second pad, the selected peroxide should be present at alevel ranging from 1.0% to 30% w/w of the total composition absorbedinto the pad. A preferred concentration is about 2% to about 3% of theselected antibiotic and about 5% to about 10% of the selected peroxide,based on the total weight of each of the compositions which are used toimpregnate the pads.

1. Aqueous Emollient Peroxide-Containing Gels

A preferred peroxide-containing composition for use on one of the padsof the present applicator system comprises an effective anti-acne amount(about 1-10%, preferably about 2.5-7.5%) of an organic peroxide,preferably benzoyl peroxide in combination with an aqueous gelcomprising water (about 40-75%), an effective amount (about 0.25- 5%) ofan inorganic gelling agent, an inorganic emollient oil plus an emollientorganic ester (2.5-10%) and, optionally, an amphoteric surfactant(0.025-0.25%) and a watermiscible organic solvent, i.e., 10-20% of a (C₂-C₄) alkanol.

a. Emollient Oils

Useful emollient oils for incorporation into the aqueous reactant phaseinclude those water-insoluble liquids which can function to soften theskin of the user and provide a degree of barrier protection againstenvironmental irritants.

Preferred emollients oils for use in the present invention includemixtures of (i) inorganic emollient oils (minerals or silicone oils)with (ii) emollient organic esters. Mineral oils are complex mixtures ofparaffin and naphthalene hydrocarbons, e.g., the C₁₈ -C₃₆ hydrocarbonmixtures available from Penreco, Butler, PA, e.g., Peneteck® technicalmineral oil (viscosity 3.4-4.7 centistokes @40° C.), the Drakeol® lightmineral oils, USP (viscosities 6.5-30.2 centistokes @40° C.) and theDrakeol® mineral oils, USP (viscosities 35.0-70.0 @40° C.). The specificgravity of mineral oils useful in the practice of the present inventionpreferably is about 0.80-0.9 at 15.6° C. (60° F.). Preferred mineraloils for use in the present vehicles are odorless, colorless (30+Sayboltcolor) and comply with FDA requirements under the Federal Food, Drug andCosmetic Act.

Silicone fluids can also be used alone or in combination with themineral oil component. Useful classes of silicone fluids include thelinear polydimethylsiloxanes or the tetrameric or pentameric cyclicsiloxanes (cyclomethicones) which are available from Rhone-Poulenc, Inc.(Monmouth Junction, N.J.) as the Rhodorsil® fluid series in a wide rangeof viscosities (i.e., 10-10,000 cps.). Fluids of about 0.5-150 cpsviscosity, preferably about 25-100 cps, are preferred. Preferably,mineral oil and/or silicone oils will make up about 0.1-1% of theperoxide-containing gelled vehicle.

Preferred emollient esters include those organic esters that can alsofunction as nonionic surfactants. They include about 0.5-5% of(polyoxyethylene) ((C₈ -C₁₂) fatty acid) esters of glycerol, such asPEG-7 glyceryl cocoate (Cetiol® HE, Henkel), PEG-30 glyceryl cocoate,PEG-12 glyceryl laurate, PEG-20 glyceryl oleate, and the like, whereinthe number designates the approximate number of oxyethylene moietiespresent.

Another preferred class of emollient ethers are the polyoxypropylene,polyoxyethylene ethers of lanolin or of (C₈ -C₂₂) fatty alcohols, suchas PP5-5-Ceteth-20 which is the ether of cetyl alcohol having 20ethylenoxy units and 5 propylenoxy units (Procetyl® AWS, Croda), andLanexol® AWS (PPG-12-PEG-50 lanolin, Croda). These mixed polyalkylenoxyethers may be present at about 0.1-0.5% of the total peroxide-containinggelled vehicle.

Other useful emollient esters include (C₅ -C₃₀)-alkyl, (C₈ -C₂₂)fattyacid esters, wherein the fatty acid moiety is optionally substitutedwith a (C₈ -C₂₂)alkanoyl group. Such esters are commercially available,e.g., as Ceraphyll® 847 [2-octyl(dodecyl)] (12-steroyl-stearate),Ceraphyll® 368 (2-ethylhexylpalmitate) and Ceraphyll® 230 (isocetylstearate) from Van Dyk & Co., Belleville, N.J. Preferably, the aqueousreactant phase will include about 5-50% by weight of these fatty acidesters, most preferably about 10-45%.

Other useful classes of water-insoluble emollient esters include the (C₈-C₂₂)fatty acid esters of propylene glycol, e.g., propylene glycoldicaprylate/dicaprate (Edenol® 302); the (C₆ -C₁₂)fatty alcohol estersof hydroxy (C₈ -C₂₂)fatty acids, e.g., octylhydroxy stearate(Naturechem® DHS); the esters of fatty alcohol(polyethylene oxideethers)with fatty acids, e.g., myreth-3-caprate, myreth-3-myristate andmyeth-3-myristate (Cetiol® 1414-E, Henkel), wherein the number indicatesthe number of oxyethylene moieties present; the benzyl alcohol esters ofone or more C₁₀ -C₂₀ fatty acids, e.g., benzyl linoleate (Dermol® 618,Alzo, Inc., Matawan, N.J.); the fatty alcohol esters of benzoic acidssuch as the C₁₂ -C₁₅ alkylbenzoates (Finsolv® TN, Finetex, Inc.)described in U.S. Pat. Nos. 4,278,655 and 4,275,222; the liquid fattyalcohol esters of C₃ -C₆ aliphatic carboxylic acids, i.e., isodecylneopentanoate (Dermol® 105); and the (C₁ -C₅)alkanol di- or triesters ofdimer or trimer acid (the dimer or trimer of oleic acid). Such estersare commercially available as Schercemol® TT (triisopropyl trimerate)and Schercemol® DID (diisopropyl dimerate, Scher Chemicals, Clifton,N.J.). The liquid fatty acid-esters of dimer acid may also besuccessfully employed in the present compositions, e.g., thediisostearyl ester of dimer acid, Schercemol® DISD.

b. Surfactant

Surfactants may also be used to stabilize the gelled composition. Apreferred class of these materials is fatty acid amides such as themono- and dialkanolamides of C₈ -C₂₂ fatty aids, e.g., a mono- or di(C₂-C₄)alkanol-amide. Commercially available, nonionic surfactants of thisclass include lauramide DEA (Standamid™ LP, Henkel), lauramide MEA(Monamid™ LMA, Mona), lauramide MIPA (Monamid™ LIPA, Mona), myrisamideMEA, myristamide MIPA, Myristamide DEA, Oleamide DEA, oleamide MEA,oleamide MIPA, cocamide MEA, cocamide DEA, cocamide MIPA, stearamideMEA, stearamide MIPA, stear-amide DEA and the like.

Other useful nonionic surfactants include the amine oxides, such as theC₁₀ -C₂₀ -alkyl-di(lower)alkyl-amine oxides or the [C₁₀ -C₂₀-alkylamido, (C₂ -C₅)alkyl]di(lower)-alkyl-amine oxides. Especiallypreferred members of this class include lauryl(dimethyl) amine oxide,myristyl(dimethyl)amine oxide, stearyl(dimethyl)amine oxide (Schercamox™DMS, Scher Chemicals, Inc., Clifton, N.J.); coco(bishydroxyethyl)amineoxide (Schercamox™ CMS), tallow(bishydroxyethyl)amine oxide andcocoamidopropyl(dimethyl)amine oxide (Schercamox® C-AA).

A further useful class of surfactants is the anionic surfactants,including the C₁₄ -C₁₈ primary alkyl sulfates, such as sodium laurylsulfate, sodium cetyl sulfate and sodium stearyl sulfate.

c. Gelling Agents

The present peroxide-containing vehicles will comprise an amount of aninorganic or organic gelling agent effective to gel or thicken theaqueous-alcoholic mixture to at least a cream- or lotion-likeconsistency.

Preferably, the inorganic gelling agents employed will comprise those ofnatural or synthetic of mineral origin. Preferred gelling agents are themontomorillonite clays such as the saponites, hectorites, laponites andthe montmorillonite colloidal clays such as Veegum™ (VanderbiltMinerals, Murray, Ky.) or Magnabrite™ (American Celloid Co., Skokie,Ill.. Clay-based gellants containing montmorillonite and aluminumhydrosilicate together with suborganic radicals are available as theTixogel™ series (United Catalysts, Louisville, Ky.). A usefulmontmorillonite clay gelling agent is a bentonite such as Korthix™ H(Kaopolite, Inc., Union, N.J.). Inosilicates can also be used, alone orin combination, with the clays. Preferred inosilicates are thenaturally-occurring calcium metasilicates such as wollastonite,available as the NYAD™ wollastonite series (Processed Minerals Inc.,Willsboro, N.Y.). Synthetic sodium magnesium silicate clays, alumina,magnesium aluminum silicate, and fumed silicas can also be used asgelling agents.

Useful organic gelling agents include microcrystalline cellulose andhydroxyalkyl cellulose ethers such as hydroxypropylmethyl cellulose(HPMC), hydroxymethyl cellulose (HMC), carboxymethyl cellulose (CMC),2-hydroxyethyl cellulose, 2-hydroxyethylmethyl cellulose, and2-hydroxypropyl cellulose (Klucel® H).

Organic gelling agents useful in the practice of the present inventionalso include polyvinylpyrrolidone and polymeric organic waxes. Theuseful polymeric waxes include ethylene acrylate copolymers, ethyleneacrylic acid copolymers and polyethylene (e.g., oxidized polyethylenes).These materials are commercially available in the form of aqueousemulsions or dispersions, e.g., from Allied Chemical, Morristown, N.J.,as the A-C Copolymer and A-C Polyethylene series, such as A-C Copolymer540, A-C Copolymer 580 and A-C Polyethylene 617 and 629. Waxypolyethylene glycols (PEG) such as those of a molecular weight of about800 to 1700-2000 are preferred for use in the present gels.

Preferred gelling agents include the so-called hydroxylated vinylicpolymers, particularly those disclosed in U.S. Pat. No. 2,798,053. Amongthose hydroxylated vinylic polymers of special interest herein aredescribed generally as interpolymers of a monomeric monoolefinic acrylicacid, and from about 0.1% to about 10% by weight based on the totalmonomer of a monomeric polyether of an oligosaccharide in which thehydroxyl groups which are modified are esterified with allyl groups withsaid polyether containing at least two allyl ether groups peroligosaccharide molecule. Commercially available interpolymers of thistype are marketed under the trade name Carbopols®. These are describedas being polymers of acrylic acid crosslined with about 1% of apolyallyl ether of sucrose having an average of 5.8 allyl groups foreach sucrose molecule. These polymers have molecular weight in the orderof magnitude of 1,000,000. Such polymers are available from the B. F.Goodrich Chemical Company and are sold under such trademarks asCarbopol® 934, Carbopol® 940, Carbopol® 941 and Carbopol® 934P.

The quantity of gelling agent that may be contained in the presentcompositions may also vary somewhat. Ordinarily, this will constituteabout 0.1% to about 15% by weight, and preferably about 0.5% to about 3%by weight, based on the total weight of the finished peroxide-containingvehicle.

A typical formulation for an aqueous-alcohol emollient benzoyl peroxidegel is given on Table I, below. The gel contains 15% isopropanol and 5%benzoyl peroxide, and has the consistency of a light gel.

                  TABLE I                                                         ______________________________________                                                      CTFA                                                            INGREDIENTS   CHEMICAL NAME*     %                                            ______________________________________                                        Water, distilled                                                                            --                 63.73                                        Laponite XLS  Sodium Lithium Magnesium                                                                         1.97                                                       Silicate                                                        Isopropanol   Isopropyl Alcohol  15.00                                        Cetiol HE     PEG-7 Glyceryl Cocoate                                                                           1.45                                         Edenol 302    Propylene Glycol Dicaprylate/                                                                    .43                                                        Dicaprate                                                       Schercemol DISD                                                                             Diisostearyl Dilinoleate                                                                         .65                                          Naturechem OHS                                                                              Octyl Hydroxystearate                                                                            .95                                          Finsolv TN    C12-15 Alcohols Benzoate                                                                         .70                                          Cetiol 1414-E Myreth-3 Myristate .16                                          Lamapon S     Potassium Coco-Hydrolyzed                                                                        .05                                                        Animal Protein                                                  Procetyl AWS  PPG-5-Ceteth-20    .15                                          Lanexol AWS   PPG-12-PEG-50 Lanolin                                                                            .15                                          Mineral Oil Light                                                                           Mineral Oil        .25                                          Schercamox C-AA                                                                             Cocamidopropylamine Oxide                                                                        .06                                          Benzoyl Peroxide (35%)                                                                      --                 14.30                                                                         100.00                                       ______________________________________                                         *See CTFA Cosmetic Ingredient Dictionary, N. F. Estrin, ed., The Cosmetic     Toiletry and Fragrance Association, Inc., pub., Washington, D.C. (3d ed.      1982).                                                                   

To prepare this formulation, the laponite is added to the water withvigorous stirring. In another vessel, the emollient oils and the amineoxide are added in the order listed with stirring, and the mixture isheated gradually to 60° C., then cooled to 25° C. The isopropanol isthen added to the water-laponite stirring with good agitation, and theresultant mixture is stirred into the emollient mixture, followed by theaddition of benzoyl peroxide.

2. Aqueous, Non-Emollient Peroxide Gels

The complex mixture of emollient esters and surfactants listed on TableI is not essential to the preparation of an aqueous benzoylperoxide-containing acne treatment gel. For example, 10-20% benzoylperoxide can be stably dispersed in about 50-80% water with the aid ofan effective amount of one or more inorganic gelling agents, e.g., 1-3,such as those useful to prepare the emollient gels above. Preferably,about 0.5-25%, most preferably about 2-20% of total gelling agent willbe used. Typical formulations for four such gels are provided in TableII, below.

                  TABLE II                                                        ______________________________________                                        CTFA             Formulation                                                  INGREDI-                                                                              CHEMICAL     A       B     C     D                                    ENTS    NAME         %       %     %     %                                    ______________________________________                                        Water   --           66.50   83.13 83.38 73.04                                Laponite                                                                              Sodium Lithium                                                                             2.06    --    --    1.80                                 XLS     Magnesium                                                                     Silicate                                                              Laponite                                                                              Sodium Lithium                                                                             --      2.57  1.81  .46                                  XLG     Magnesium                                                                     Silicate                                                              Veegum  Magnesium    --      --    0.51  --                                   HV      Aluminum                                                                      Silicate                                                              Dispal  Aluminum Oxide                                                                             17.14   --    --    --                                   Alumina Dispersion                                                            23N4-20                                                                       Sol.                                                                          Dispal  Aluminum Oxide                                                                             --      --    --    10.40                                Alumina                                                                       23N4-80                                                                       Powder                                                                        Benzoyl --           14.30   14.30 14.30 14.30                                Peroxide                                                                      (35%)                                                                         Total                100.00  100.00                                                                              100.00                                                                              100.00                               ______________________________________                                         Gels A, B and D are thick/viscous gels. Gel C is thixotropic, in that it      fluidizes when subjected to shear.                                       

3. Anhydrous Emollient Peroxide Gel

The benzoyl peroxide gel component of the present invention can also beprepared by dispersing the benzoyl peroxide in an essentiallywater-alcohol free blend of surfactants, along with about 1-10% of theinorganic gelling agent. Such gels can comprise about 75-90% of amixture of inorganic and organic emollient oils, about 1-10% peroxideand, optionally, above 0.1-1% of amine oxide or other amphotericsurfactant. The inorganic oil is preferably a minor proportion, i.e.,about 1-7.5% of the finished gel. A typical formulation for such a gelis given in Table III below.

                  TABLE III                                                       ______________________________________                                                      CTFA                                                            INGREDIENTS   CHEMICAL NAME*     %                                            ______________________________________                                        Cetiol HE     PEG-7 Glyceryl Cocoate                                                                           23.64                                        Edenol 302    Propylene Glycol   7.01                                                       Dicaprylate/Dicaprate                                           Schercemol DISD                                                                             Diisostearyl Dilinoleate                                                                         10.51                                        Naturechem OHS                                                                              Octyl Hydroxystearate                                                                            15.49                                        Finsolv TN    C12-15 Alcohols Benzoate                                                                         12.80                                        Cetiol 1414-E Myreth-3 Myristate 2.61                                         Lamapon S     Potassium Coco-Hydrolyzed                                                                        0.81                                                       Animal Protein                                                  Procetyl AWS  PPG-5-Ceteth-20    4.07                                         Mineral Oil Light                                                                           Mineral Oil        4.07                                         Schercamox C-AA                                                                             Cocamidopropylamine Oxide                                                                        0.49                                         Cabosil M-5   Amorphous Silica   4.20                                         Benzoyl Peroxide (35%)                                                                      --                 14.30                                        Total                            100.00                                       ______________________________________                                    

These gels are "anhydrous" in the sense that the only water or alcoholpresent is provided via the commercially available forms of theemollient esters and surfactants, and is preferably ≦5% of the totalgel.

II. Antibiotic

Preferred dual pad applicators intended for acne treatment will comprisea pad having an absorbed aqueous, alcoholic, or aqueous-alcoholicsolution of the antibiotic, of which erythromycin, tetracycline,clindamycin and the pharmaceutically acceptable salts thereof arepreferred. Useful salts include the salts of inorganic or organic acids,such as the hydrochloride, phosphate, glyconate, citrate, maleate,stearate, and hydrobromide salts. Useful alcohols include ethanol,isopropanol and mixtures thereof. Benzyl alcohol and/or butanol can alsobe used in combination with varying amounts of water. All, or a part ofthe alcohol, can be replaced by other volatile water-miscible organicsolvents such as propylene glycol, m-pyrol, liquid polyethylene glycols,acetone, THFA and the like.

The antibiotic or salt thereof will preferably be dissolved or dispersedin the solvent or solvent system at a concentration effective tosignificantly decrease the skin concentration of Corynebacterium acnesupon topical application of about 0.5-5.0 mls of the antibiotic solutionfor the skin of the afflicted human or animal, e.g., an about 0.5%-5%solution or dispersion of the antibiotic in the solvent or solventsystem is preferred.

Emollient organic esters are preferably also self-emulsified into anaqueous alcohol system, e.g., one comprising about 80-95% aqueousalcohol, about 5-15% emollient organic ester, and about 0.1-5%antibiotic, in order to provide the pad with a better skin-feel and toaid in the even distribution of the antibiotic on the skin. A typicalemollient formulation comprising 1.0% clindamycin phosphate, is given onTable IV, below.

                  TABLE IV                                                        ______________________________________                                        Ingredient        Percent                                                     ______________________________________                                        Water             20.0                                                        Isopropanol       70.3                                                        10% NaOH          0.7                                                         Clindamycin phosphate                                                                           1.0                                                         Emollient Esters                                                              Cetiol HE         2.3                                                         Myritol 318*      0.7                                                         Naturechem GTR**  1.5                                                         Finsolv TN        2.8                                                         Cetiol 144-E      0.3                                                         Procetyl AWS      0.5                                                         ______________________________________                                         *Caprylic/Capric Triglyceride                                                 **Glyceryl triacetyl ricinoleate                                         

To prepare this formulation, clindamycin phosphate is dissolved in thewater at 25° C. and isopropyl alcohol added, this solution is added to apreformed blend of the emollient esters and the pH of the mixture isadjusted to 6.8 with 10% NaOH.

Erythromycin can replace clindamycin in this formulation.

III. Salicylic Acid

In dual pad applicator packs intended for acne treatment, the antibioticor benzoyl peroxide composition can be replaced with a compositioncontaining salicylic acid, which acts as an antiseptic, an antifungaland a topical keratolytic agent. A suitable vehicle for salicylic acidcan be prepared by mixing water with a gelling agent and adding awater-miscible organic solvent in a weight ratio of about 0.1-4 partswater to 1.0 part solvent, e.g., a (C₂ -C₄)-alkanol. The salicylic acidis dispersed in this mixture at about 0.5-10% of the finishedcomposition. Two typical salicylic acid formulations are given on TableV, below.

                  TABLE V                                                         ______________________________________                                                   CTFA            A        B                                         Ingredients                                                                              Chemical Name   %        %                                         ______________________________________                                        Water,     --              74.57    12.62                                     distilled                                                                     Klucel H   Hydroxypropylcellulose                                                                        1.52     --                                        Carbopol 934P                                                                            Carbomer 934P   --       1.95                                      NF                                                                            Isopropanol                                                                              Isopropyl Alcohol                                                                             21.74    82.52                                     Salicylic Acid                                                                           --              2.17     2.91                                      Powder U.S.P.                                                                 Total                      100.00   100.00                                    ______________________________________                                         Formulation B yielded a light, fluid gel that spread into an even film.       Formulation A yielded a thicker, fluid gel.                              

IV. Retinoic Acid

As disclosed hereinabove, for the topical treatment of acne using thepresent dispensing an applicator system, one of the pads can beimpregnated with a liquid, semi-liquid or gelled formulated comprisingan effective anti-acne amount of retinoic acid, while the other pad orpads preferably contain an emollient composition to counteract thedrying/scaling properties of the retinoic acid, and/or an effectiveamount of a sunscreen composition to protect the user from retinoicacid-induced sensitivity to UV light.

Useful retinoic acid compositions can be formulated as creams, gels, orliquids; preferably comprising about 0.01-0.25 wt-% of retinoic acid.Useful gels can be formed in aqueous, water-miscible organic solventvehicles comprising water:solvent ratios of about 9:1 to 1:9, incombination with an effective amount of an organic and/or inorganicgelling agent, of the classes described hereinabove. Retinoicacid-containing liquids can simply be prepared by dissolving aneffective amount of retinoic acid in water organic solvent, usingnontoxic organic solvents, such as the (C₂ -C₄)alkanols and liquidpolyoxyethylene glycols disclosed hereinabove. Due to the unstablenature of retinoic acid, minor but effective amounts of anti-oxidants,such as BHT, are preferably included in these formulations.

V. Skin Moisturizing Composition/Sunscreens

Emollient compositions which soften and protect the skin are preferablyused in conjunction with a dermatological composition comprisingretinoic acid, or as a carrier vehicle for retinoic acid. When used inconjunction with retinoic acid, the emollient compositions preferablyinclude an effective amount, i.e., 1-10 wt-% of one or more, i.e., 1-3sunscreen compounds. These include oxybenzone,ethyldihydroxypropyl-p-amino benzoate, octyl dimethyl-p-aminobenzoate,para-aminobenzoic acid, and the like. Useful emollient compositionsinclude those disclosed in Smith et al. (U.S. Pat. No. 4,559,157) whichare oil-in-water emulsions comprising an oil phase containing at leastone emollient oil and at least one emollient wax stabilizer, dispersedin an aqueous phase comprising at least one polyhydric alcohol emollientand at least one amphoteric (amine oxide) or anionic surfactant.Effective amounts of bactericidal preservatives and fragrance may alsobe employed in the impregnating emulsion. These emulsions are formulatedso that an effective amount of emollients and fragrance is released andevenly coated onto the skin with no "skipping" or separation when theimpregnated pad is pressed or rubbed against a moist skin surface. Thisrequires that the emulsion be formulated so that it will be stable andnot break when mixed with the additional water present on the skin dueto bathing, showering or the like.

It has been found that emollient emulsions stable under these conditionscan be formulated by dispersing an oil phase comprising one or moreemollient oils and one or more emollient wax stabilizers in an aqueousphase comprising one or more polyhydric alcohol emollients and one ormore water-soluble organic surfactants.

Therefore, the emulsions of the present invention preferably willcomprise about 15-50% of water-insoluble or soluble active ingredients,i.e., the emollients, surfactants, fragrance and preservatives; and50-85% water, preferably distilled or deionized water. About 7-20% ofthe active ingredients will be present as the oil phase of the emulsion,while the remainder of the active ingredients will be fully soluble inthe water phase. Emollients will preferably comprise about 10-50% byweight of the emulsions. Emollients useful in the practice of thepresent invention are generally described by G. Barnet, Emollient Creamsand Lotions, and by S. J. Strianze, Hand Creams and Lotions, inCosmetics--Science and Technology, Wiley Interscience Pub. (1957) atpages 99-181.

A. Emollient Wax Stabilizer

The emollient oils useful in these compositions have been describedhereinabove. Emollient wax stabilizers are waxy solids at roomtemperature. They function to soften and smooth the skin surface and toprevent evaporation of interior skin moisture. They also can function asnonionic emulsifying agents and act to adjust the final viscosity of thecomposition. The emollient wax stabilizers useful in the practice of thepresent invention include beeswax, spermaceti, solid hydrocarbons, C₁₂-C₁₈ fatty alcohols, glyceryl monostearate, ethylene glycolmonostearate, polyethylene glycol distearate and other (C₁₂ -C₁₈)fattyacid-(C₂ -C₅) polyol esters. Particularly useful in the practice of thepresent invention are the fatty alcohols, such as lauryl, cetyl, oleyland stearyl alcohols or mixtures thereof, and the fatty acid-polyolesters, i.e., glyceryl monostearate, which is commercially available asCerasynt® Q from Van Dyk & Co., Belleville, N.J. In one class ofemulsions useful in the practice of the present invention, all or a partof the emollient oil, isostearyl neopentanoate, or Ceraphyll® 375, isreplaced with one of the emollient waxes of the Softisan® Series(Dynamit Nobel Chemicals, Rockleigh, N.J.), a fragrant emollient esterof the class of compounds designated as triglycerides of C₁₀ -C₁₈saturated fatty acids, which allows the use of less fragrance, thusresulting in a cost savings. An especially useful member of this seriesis Softisan® 100. Preferably, emollient waxes will make up about 3-10%of the composition, most preferably about 3.5-8%.

B. Polyhydric Alcohol Emollient

The emulsions of the present invention will also include one or morepolyhydric alcohol emollients which are preferably C₂ -C₅ alkanolssubstituted with 2-4 hydroxyl groups, such as propylene glycol,glycerol, and sorbitol. Polyhydric alcohol emollients will preferablymake up 5-15% by weight of the emulsion. One especially preferredmixture of polyhydric alcohol emollients is an about 1:1 mixture ofpropylene glycol and glycerol.

Therefore, preferred emulsions useful in the present invention may beformulated so as to contain about 50-85% water, about 4-12% emollientoil, about 3.0 -10% emollient wax stabilizer, about 5-20% polyhydricalcohol emollient, and about 0.5%-10% organic, water-soluble surfactant,and optionally, about 0.025-0.75% antibacterial preservative and about0.1 to 0.5% fragrance.

The following ingredients were combined in the weight percentagesindicated in Table VI to form a moisturizing composition by theprocedure described below.

                  TABLE VI                                                        ______________________________________                                        INGREDIENT         PERCENT     GRAMS                                          ______________________________________                                        Group A                                                                       Glyceryl Monostearate                                                                            5.0         750.0                                          Cetyl Alcohol      0.5         75.0                                           Mineral Oil        5.0         750.0                                          i-Stearyl Neopentanoate                                                                          3.0         450.0                                          Propyl Parabens    0.10        15.0                                           Butyl Parabens     0.05        7.5                                            Group B                                                                       Water (deionized)  62.15       9,322.5                                        Methyl Parabens    0.30        45.0                                           Propylene Glycol   5.00        750.0                                          Glycerol           5.00        750.0                                          Lauryl Dimethyl Amine Oxide                                                                      3.0         450.0                                          (29-31% Solution in H.sub.2 O)                                                Group C                                                                       Water              5.0         750.0                                          Sodium Lauryl Sulfate                                                                            0.50        75.0                                           Fragrance          0.30        45.0                                           Water              5.0         750.0                                          Kathon CG          0.10        15.0                                           (Preservative)                                                                                   100.00      15,000.0                                       ______________________________________                                    

The oil-phase ingredients of Group A were mixed and heated to 75° C. Thewater-phase Group B ingredients were separately mixed, heated to 75° C.and then the Group A ingredients were added with good agitation.Stirring was contained for 10 minutes and a 23° C. solution of the GroupC ingredients was added subsurface to the stirred 72° C. mixture. Theemulsion was stirred and cooled to 45° C. at which point the fragrancewas added. The mixture was stirred until its temperature fell to 35° C.The mixture was allowed to stand overnight and then the preservativesolution was added with stirring. The mixture was stirred for 45 minutesand then used to impregnate a sheet of Crown Textile C-785 (1.25 oz/yd²)via a Meyer Rod to form a one-use cosmetic applicator pad (0.25 g per1.5 square inches of fabric).

The resultant applicator pads were moist but not sticky or unduly wet tothe touch and readily applied a clear, non-sticky, homogenous film ofthe emollient emulsion to dry skin surfaces. The film retained thesedesirable characteristics when the skin was moistened prior to use ofthe applicator. As noted above, an effective anti-acne amount ofretinoic acid can optionally be combined with this emollientcomposition.

V. Make-Up Remover

The present applicator system can also be used as a dual systemapplicator wherein one or more pads are used to apply one or more of thepigment-containing cosmetic compositions variously known as "make-up,"i.e., lipstick, rouge, blush, eyeshadow, eyeliner and the like, whileanother of the pad or pads is impregnated with a composition that willremove the make-up, e.g., will solubilize the waxy components, or waxybase, of the make-up and cause it to be absorbed by the porousapplicator pad.

A preferred make-up remover composition is disclosed in Kellett (U.S.Pat. No. 4,806,572) and comprises a wax-free mixture of about 25-75%water, about 15-70% of a water-insoluble liquid emollient oil (asdescribed hereinabove) and an amount of surfactant (about 1-15%)effective to stabilize the aqueous phase as a homogeneous emulsion.Preferred emollient oils comprise a mixture of a mineral oil and aliquid fatty acid ester, i.e., a (C₅ -C₃₀)alkyl (C₈ -C₁₂)-fatty acidester. Preferably, the surfactant is a mixture of an anionic surfactantwith a nonionic polyoxyalkylene block copolymer (mw 1500-3500) in aweight ratio of about 1.5-0.75:1.

Preferred make-up remover pads comprise a resilient open-celled,hydrophilic polyurethane foam matrix, wherein said matrix integrallyincorporates an aqueous phase incorporating about 25-75% water, about15-70% of a water-insoluble liquid emollient oil, and an amount ofsurfactant effective to stabilize the aqueous phase so that it isreleased from the foam matrix as a homogenous emulsion when the pad isapplied to skin, and wherein said aqueous phase contains no natural orsynthetic wax.

VI. Steroids

To treat skin irritations and other dermatological conditions such asvarious dematoses, including chronic neurodermatitis, nummulardermatitis, atopic dermatitis, and psoriasis; eczema, poison plantrashes, insect bites and rashes due to cosmetics, detergents, jewelryand the like, one or more of the pads of the present applicators can beimpregnated with an effective dermatological amount of one or moresteroids, such as a corticosteroid. The pad may be impregnated with adry powder of the steroid or steroids, optionally in combination with asolid inert carrier such as starch, talcum powder, dextrin,microcrystalline cellulose and the like. Preferably, the steroid isimpregnated into the pad in combination with a pharmaceuticallyacceptable carrier, i.e., in combination with a suitable solvent orsolvent mixture (in solution), a liquid lotion or emulsion, or anointment or a gel.

The percentage of the steroid present in the vehicle can be variedwidely, depending on the potency of the steroid with respect to thecondition to be treated, but can range from about 0.025-0.05% in thecase of corticosteroids such as betamethasone dipropionate orfluocinonide, up to as much as 1-5% in the case of hydrocortisone orcortisol.

Useful corticosteroids, their dermatological indications and dosages aredisclosed in Remington's Pharmaceutical Sciences, A. Osol, ed., MackPublishing, Easton, Pa. (16th ed. 1980) at pages 898-912, which isincorporated by reference herein, and include betamethasone, cortisol,dexamethasone, flumethasone fluocinolone, fluorometholone,flurandrenolide, methylprednisolone, prenisolone, desoximetasone,diflorasone, triamcinolone, and their nontoxic organic acid salts suchas the benzoate, acetate, valerate, pivalate, acetonide,acetonide-acetate, diacetate, butyrate, dipropionate and valerate salts,and the like.

In combination with the appropriate carrier, if any, the steroid will beimpregnated into the applicator pad so that, upon application of the padto the afflicted skin area, an effective amount of steroid will bedelivered to the skin, e.g., from about 500 μg-250 mg of total steroidper m² of skin, depending upon the steroid or steroids present in thecomposition.

Two representative steroid-containing solutions comprising mixtures oforganic solvents as the carrier vehicle are given in Table VII below.

                  TABLE VII                                                       ______________________________________                                        Steroid Solutions                                                                                Formulation                                                                   (wt-%)                                                     Ingredient           A      B                                                 ______________________________________                                        Propylene glycol     86.18  82.95                                             Isopropyl alcohol    12.00  7.00                                              m-Pyrrol             1.75   --                                                Carbitol             --     10.00                                             Betamethasone dipropionate                                                                         0.64   --                                                Fluocinonide (Lidex ™)                                                                          --     0.05                                              ______________________________________                                    

The steroid can also be microencapsulated or stabilized by absorptiononto or into dextrin or cyclodextrin particles by methods known to theart.

As noted above, when a steroid-containing composition is included in oneof the pads, the other pad or pads can contain dermatological agentswhich complement or enhance the activity of the steroid. Suchingredients include antihistamines, antibiotics, e.g., in combinationwith the carrier vehicles described above, emollient compositions suchas those disclosed above, anti-fungal agents, sunscreens as disclosedabove, and compositions which will enhance penetration of the steroidinto the skin. The latter compositions include those which, followingtheir application, form an occlusive barrier or film over the appliedfilm of steroid-containing composition. Such barrier-formingcompositions include those which comprise solvent-dissolved or dispersedfilm-forming polymers such as polysaccharides, polyvinylalcohols,polyacrylate salts, and/or cross-linked polyacrylate hydrogels.

Any of the above-described compositions can be preformulated and appliedto the pads, which have been preattached to the base or cover sheet, bydipping, spraying or brushing techniques well known to the art.

In practice, the user, e.g., a human afflicted with acne, would eitherexpose the medicated pads and apply them sequentially or simultaneouslyto the afflicted area. For example, the user might first expose a padimpregnated with Retin® A or an anti-acne antibiotic, i.e., erythromycinor clindamycin or a pharmaceutically acceptable salt thereof, eitherdissolved in a non-toxic organic solvent, or dispersed in a gelledvehicle, such as that described in conjunction with Table IV, above.After applying the antibiotic pad to the afflicted skin area, the userwould expose the second pad impregnated with peroxide in one of thevehicles described in conjunction with Tables I-III, above, or a padimpregnated with salicylic acid-containing vehicle. This same skin areawould then be contacted with the second pad, in order to combine the twoactive ingredients in situ. Alternatively, the user could expose twoadjacent pads, and apply the adjacent pads essentially simultaneously tothe skin, to deposit, for example, a mixture of antibiotic- andperoxide-containing vehicles thereto, preferably in a homogeneous, evenfilm.

Each composition will be absorbed into a single pad in an amounteffective to provide a unit dosage of each of the bioactive ingredientstherein. It is to be understood that such a dose can vary widely, as itwill be based on the size of skin area to be treated, and the nature andseverity of the dermatological condition to be treated. For example, theamount of a given liquid, semi-liquid or gelled composition delivered tothe skin of the user may vary from as little as 0.25-0.5 g to as much as1-3 g, depending upon the choice of active ingredient, the size of padand type of material of which it is constructed and the skin area andcondition to be treated. Thus, the amount of active ingredient deliveredas a unit dose can be preselected, using the weight percentages providedhereinabove as guidelines.

All patents, patent applications and other documents cited hereinaboveare incorporated by reference herein. The invention has been describedwith reference to various specific and preferred embodiments andtechniques. However, it should be understood that many variations andmodifications may be made while remaining within the spirit and scope ofthe invention, and the invention is not to be construed as limited tothe specific embodiments shown in the drawings.

What is claimed is:
 1. A method for applying a plurality ofdermatological agents to the skin from one dispensing and applicatorsystem comprising the steps of:(a) providing a dispensing and applicatorsystem comprising:(1) a first and second flexible, moisture impermeablecover sheet; (2) a first applicator pad and a second applicator padaffixed to a first surface of said first and second cover sheets,respectively; said first pad being impregnated with a first compositioncomprising a first dermatological agent and said second pad beingimpregnated with a second composition comprising a second dermatologicalagent; and (3) a flexible, moisture impermeable support sheet having theperipheral surface of its first side releasably sealed by means of afirst continuous seal line to the opposed peripheral surface of thefirst cover sheet so as to form a first compartment containing the firstpad attached t said surface of first cover sheet; and having theperipheral surface of its second side releasably sealed by means of asecond continuous seal line to the opposed peripheral surface of thesecond cover sheet so as to form a second compartment containing saidsecond pad attached to said second cover sheet, which seal lines arepositioned inwardly from the edges of the sheets over a portion of theopposed peripheral surfaces, so as to form two pairs of opposed flanges;(b) sequentially manually grasping and separating each pair of opposedflanges to at least partially release each cover sheet from the supportsheet, so that said first pad and said second pad are exposed; and (c)contacting said first pad and said second pad with the skin to releasethe compositions sequentially from the pads, to thereby apply a film ofthe agents onto the skin.
 2. A method for applying a plurality ofdermatological agents to the skin from one dispensing and applicatorsystem comprising the steps of:(a) providing a dispensing and applicatorsystem comprising:(1) a first and second flexible, moisture impermeablecover sheet; (2) a first and second applicator pad each affixed to afirst surface of said first and second cover sheets, respectively, saidfirst pad being impregnated with a first composition comprising a firstdermatological agent and said second pad being impregnated with a secondcomposition comprising a second dermatological agent; and (3) aflexible, moisture impermeable support sheet having the peripheralsurface of its first side releasably sealed to the opposed peripheralfirst surface of the first cover sheet by a first continuous seal line,so as to form a first compartment containing the first pad attached tosaid first surface of the first cover sheet; and said second cover sheethaving the peripheral surface of its first surface releasably sealed tothe opposed second peripheral surface of the second surface of the firstcover sheet by a second continuous seal line, so as to form a secondcompartment containing said second pad attached to the first surface ofsaid second cover sheet, which seal lines are positioned inwardly fromthe edges of the sheets over a portion of the opposed peripheralsurfaces, so as to form two pairs of opposed flanges; (b) sequentiallymanually grasping and separating each of the pairs of flanges to releasethe second cover sheet from the first cover sheet and then to releasethe first cover sheet from the support sheet, so that said pads areexposed; and (c) contacting the pads with the skin to release thecompositions sequentially from the pads, to thereby apply a film of thecompositions onto the skin.
 3. A method for applying a plurality ofdermatological agents to the skin from one dispensing and applicatorsystem comprising the steps of:(a) providing a dispensing and applicatorsystem comprising:(1) a flexible, moisture impermeable support sheethaving a first side and a second side; (2) a first applicator padaffixed to the first side of said support sheet, and a second applicatorpad attached to the second side of said support sheet, said first padbeing impregnated with a first composition comprising a firstdermatological agent and said second pad being impregnated with a secondcomposition comprising a second dermatological agent; and (3) a firstflexible, moisture impermeable cover sheet having a first peripheralsurface of a first side releasably sealed by a continuous seal line tothe peripheral surface of the first side of said support sheet; and asecond flexible moisture impermeable cover sheet, having a firstperipheral surface of a first side releasably sealed by a continuousseal line to the peripheral surface of the second side of said supportsheet; so as to form two compartments each containing one of said pads,each compartment being defined by a continuous seal line, which seallines are positioned inwardly from the edges of the sheets over aportion of the opposed peripheral surfaces, so as to form two pairs ofopposed flanges; (b) sequentially manually grasping and separating eachpair of the flanges to release each cover sheet from the support sheet,so that said pads are exposed; and (c) contacting the pads with the skinto release the compositions sequentially from the pads, to thereby applya film of the compositions onto the skin.
 4. The method of claims 1, 2or 3 wherein the cover sheet and support sheet are made of a deformableplastic coated foil.
 5. The method of claims 1, 2 or 3 wherein the coversheet and the support sheet are sealed together by heat sealing or by anadhesive.
 6. The method of claims 1, 2 or 3 wherein the applicator padsare made of natural fiber, synthetic fiber or foam.
 7. The method ofclaims 1, 2 or 3 wherein the first dermatological agent is an effectiveanti-acne amount of a peroxide.
 8. The method of claim 7 wherein thefirst dermatological agent comprises benzoyl peroxide.
 9. The method ofclaim 7 wherein the first applicator pad is impregnated with a firstcomposition comprising an effective anti-acne amount of an organicperoxide in combination with an aqeuous gel comprising about 40-75%water, about 0.25-5% of an inorganic gelling agent, and about 2.5-10% ofa mixture of an inorganic emollient oil and an emollient organic ester.10. The method of claim 9 wherein the first composition furthercomprises about 0.025-0.25% of an amphoteric surfactant.
 11. The methodof claim 10 wherein the first composition further comprises about 10-20%of a (C₂ -C₄)alkanol.
 12. The method of claim 7 wherein the firstapplicator pad is impregnated with a first gelled composition comprisingan effective anti-acne amount of an organic peroxide dispersed in about50-80% water in combination with an effective amount of an inorganicgelling agent.
 13. The method of claim 7 wherein the first applicatorpad is impregnated with a first gelled anhydrous composition comprisingan effective anti-acne amount of an organic peroxide, about 75-90% of amixture of inorganic and organic emollient oils, and about 1-10% of aninorganic gelling agent.
 14. The method of claim 13 wherein thecomposition further comprises about 0.1-1% of an amphoteric surfactant.15. The method of claim 7 wherein the second dermatological agent is aneffective anti-acne amount of an antibiotic selected from the groupconsisting of erythromycin, tetracycline, clindamycin and thepharmaceutically acceptable salts thereof.
 16. The method of claim 15wherein the antibiotic is clindamycin or a pharmaceutically acceptablesalt thereof.
 17. The method of claim 15 wherein the second compositioncomprises about 0.1-5% of the antibiotic dissolved or dispersed inmixture of water and a water-miscible organic solvent.
 18. The method ofclaim 17 wherein the second composition comprises an emulsion of about0.1-5% clindamycin, erythromycin or a pharmaceutically acceptable saltthereof, about 80-95% aqueous alcohol and about 5-15% emollient organicesters.
 19. The method of claims 1, 2 or 3 wherein the firstdermatological agent is an effective keratolytic amount of salicylicacid.
 20. The method of claim 19 wherein the first composition comprisesan aqueous-alcohol gel comprising about 0.5-10% salicylic acid.
 21. Themethod of claim 20 wherein the gel comprises about 0.5-5% of an organicgelling agent.
 22. The method of claims 1, 2, or 3 wherein the firstdermatological agent is an effective anti-acne amount of retinoic acid.23. The method of claim 22 wherein the first dermatological compositioncomprises about 0.01-0.25% retinoic acid.
 24. The method of claim 23wherein the first dermatological composition further comprises a gelledmixture of water with a water-miscible organic solvent.
 25. The methodof claim 22 wherein the first dermatological composition comprises about0.01-25% retinoic acid, about 50-85% water, about 4-12% emollient oil,about 3-10% emollient wax stabilizer, about 5-20% polyhydric alcoholemollient and about 0.5-10% organic, water-soluble surfactant.
 26. Themethod of claim 22 wherein the second dermatological compositioncomprises an effective amount of one or more sunscreen compounds. 27.The method of claim 22 wherein the second dermatological compositioncomprises about 50-85% water, about 4-12% emollient oil, about 3-10%emollient wax stabilizer, about 5-20% polyhydric alcohol emollient andabout 0.5-10% organic, water-soluble surfactant.
 28. The method ofclaims 1, 2 or 3 wherein the first dermatological composition comprisesan effective amount of one or more sunscreen compounds.
 29. The methodof claim 27 wherein the second dermatological composition comprises aneffective amount of one or more sunscreen compounds.
 30. The method ofclaims 1, 2 or 3 wherein the first composition is a pigment-containingwax-based cosmetic composition and the second composition is a make-upremover composition comprising a wax-free mixture of about 25-75% water,about 15-70% of a water-insoluble liquid emollient oil and an amount ofa surfactant effective to stabilize the mixture as a homogeneousemulsion.
 31. The method of claim 30 wherein the first applicator pad isa hydrophilic polyurethane foam pad.
 32. The method of claim 7 whereinthe first dermatological agent is an effective dermatological amount ofcorticosteroid.
 33. The method of claim 32 wherein the corticosteroid isdispersed throughout the first applicator pad as a powder.
 34. Themethod of claim 32 wherein the first applicator pad is impregnated witha corticosteroid in combination with a pharmaceutically acceptablecarrier.
 35. The method of claim 32 wherein the second dermatologicalagent is an antihistamine, an antibiotic, an antifungal agent, asunscreen, an emollient or a film-forming polymer.